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Theophylline cocrystals prepared by spray drying: physicochemical properties and aerosolization performance
Luleå University of Technology, Department of Health Sciences, Medical Science.
Luleå University of Technology, Department of Health Sciences, Medical Science.
Department of Pharmaceutics, School of Pharmacy, University College London.
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent.
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2013 (English)In: AAPS PharmSciTech, ISSN 1530-9932, E-ISSN 1530-9932, Vol. 14, no 1, 265-276 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC > THF-URE > THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.

Place, publisher, year, edition, pages
2013. Vol. 14, no 1, 265-276 p.
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Other Health Sciences
Research subject
Health Science
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URN: urn:nbn:se:ltu:diva-15810DOI: 10.1208/s12249-012-9883-3Local ID: f5eab951-e3b2-4449-b860-3e53ef2c821bOAI: oai:DiVA.org:ltu-15810DiVA: diva2:988785
Note
Validerad; 2013; 20130110 (andbra)Available from: 2016-09-29 Created: 2016-09-29 Last updated: 2017-11-21Bibliographically approved

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